Synergistic Effects of Ischemia and β-Amyloid Burden on Cognitive Decline in Patients With Subcortical Vascular Mild Cognitive Impairment | Cerebrovascular Disease | JAMA Psychiatry | JAMA Network
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Original Investigation
April 2014

Synergistic Effects of Ischemia and β-Amyloid Burden on Cognitive Decline in Patients With Subcortical Vascular Mild Cognitive Impairment

Author Affiliations
  • 1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 2Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea
  • 3Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea
  • 4Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea
  • 5Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 6Department of Neurology, Inha University School of Medicine, Incheon, Korea
  • 7Department of Biomedical Engineering, Hanyang University, Seoul, Korea
  • 8Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 9Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 10Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 11Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 12Institute for Stroke and Dementia Research, Ludwig-Maximilians University, Munich, Germany
  • 13Department of Brain Repair and Rehabilitation, University College London Institute of Neurology, Queen Square, London, England
  • 14Department of Radiology, University of California, San Francisco
  • 15Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, California
JAMA Psychiatry. 2014;71(4):412-422. doi:10.1001/jamapsychiatry.2013.4506
Abstract

Importance  Cerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and β-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins.

Objective  To determine the synergistic effects of β-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI).

Design, Setting, and Participants  A cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes.

Main Outcomes and Measures  We measured β-amyloid burden using positron emission tomography with carbon 11–labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients’ cognitive impairment.

Results  On evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI.

Conclusions and Relevance  Most patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase β-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.

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